The aim of these studies is to provide detailed understanding of the mechanisms which control the rate of hemoglobin synthesis in the maturing mammalian erythroid cell. Emphasis will be placed in elucidating the non-messenger RNA factors which moderate the rate of protein synthesis and which influence the type of the protein synthesized. These studies will make use of both animal and humaa erythroid cell experimental reticulocyte cell-free systems in order to specifically study the roles of robosomal proteins, intracellular environmental factors, hemoglobin and globin polypeptide subunits, and the external cell membrane in changing the rates and proportions of specific proteins synthesized. A special area of study will be the further delineation of the function of the ribosomes bound to the erythroid cell membrane in synthesizing nonglobin protein. The studies of he role of the erythroid cell membrane in moderating the rate and type of protein synthesis will be expanded to include its role in the destruction of the erythroid cell. In particular the role of unbalanced globin synthesis on cell membrane function, and its relationship to viability and nonviability of erythrocytes will be investigated. With respect to the human hemoglobinopathies, the effect of excess alpha and beta hemoglobin chains, which result from unbalanced globin chain synthesis, on cell membrane metabolism will be studied. These studies will be a continuation of investigation of lipid metabolism in erythroid cell membranes which have shown an effect on synthesis of membrane lipid by a variety of chemical or physical agents. The role of the cell membrane in protecting the cell from destruction when it is injured or exposed to stress situations will be accomplished by determining patterns of quantitative and qualitative lipid synthesis when erythroid cells are exposed to a variety of chemical and physical agents, and in cells in which the defective cell membrane is known to be a contributing cause to hemolytic anemia.